Cargando…
Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial
BACKGROUND: Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (C(max)). This study evaluated the drug interaction potential of...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378442/ https://www.ncbi.nlm.nih.gov/pubmed/22429273 http://dx.doi.org/10.1186/1472-6904-12-8 |
_version_ | 1782236036729929728 |
---|---|
author | Kothare, Prajakti A Seger, Mary E Northrup, Justin Mace, Kenneth Mitchell, Malcolm I Linnebjerg, Helle |
author_facet | Kothare, Prajakti A Seger, Mary E Northrup, Justin Mace, Kenneth Mitchell, Malcolm I Linnebjerg, Helle |
author_sort | Kothare, Prajakti A |
collection | PubMed |
description | BACKGROUND: Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (C(max)). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use. METHODS: This trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30(®)]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period. RESULTS: Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) C(max )reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in C(max )reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial. CONCLUSIONS: The observed reduction in C(max )is likely of limited importance given the unaltered oral contraceptive bioavailability and trough concentrations; however, for oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before exenatide injection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00254800. |
format | Online Article Text |
id | pubmed-3378442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-33784422012-06-20 Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial Kothare, Prajakti A Seger, Mary E Northrup, Justin Mace, Kenneth Mitchell, Malcolm I Linnebjerg, Helle BMC Clin Pharmacol Research Article BACKGROUND: Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (C(max)). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use. METHODS: This trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30(®)]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period. RESULTS: Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) C(max )reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in C(max )reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial. CONCLUSIONS: The observed reduction in C(max )is likely of limited importance given the unaltered oral contraceptive bioavailability and trough concentrations; however, for oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before exenatide injection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00254800. BioMed Central 2012-03-19 /pmc/articles/PMC3378442/ /pubmed/22429273 http://dx.doi.org/10.1186/1472-6904-12-8 Text en Copyright ©2012 Kothare et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kothare, Prajakti A Seger, Mary E Northrup, Justin Mace, Kenneth Mitchell, Malcolm I Linnebjerg, Helle Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
title | Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
title_full | Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
title_fullStr | Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
title_full_unstemmed | Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
title_short | Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
title_sort | effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378442/ https://www.ncbi.nlm.nih.gov/pubmed/22429273 http://dx.doi.org/10.1186/1472-6904-12-8 |
work_keys_str_mv | AT kothareprajaktia effectofexenatideonthepharmacokineticsofacombinationoralcontraceptiveinhealthywomenanopenlabelrandomisedcrossovertrial AT segermarye effectofexenatideonthepharmacokineticsofacombinationoralcontraceptiveinhealthywomenanopenlabelrandomisedcrossovertrial AT northrupjustin effectofexenatideonthepharmacokineticsofacombinationoralcontraceptiveinhealthywomenanopenlabelrandomisedcrossovertrial AT macekenneth effectofexenatideonthepharmacokineticsofacombinationoralcontraceptiveinhealthywomenanopenlabelrandomisedcrossovertrial AT mitchellmalcolmi effectofexenatideonthepharmacokineticsofacombinationoralcontraceptiveinhealthywomenanopenlabelrandomisedcrossovertrial AT linnebjerghelle effectofexenatideonthepharmacokineticsofacombinationoralcontraceptiveinhealthywomenanopenlabelrandomisedcrossovertrial |